1. Field of the Invention
The present invention relates to a process for preparing 2,2-difluoroethylamine, starting from 2,2-difluoro-1-chloroethane and ammonia.
2. Description of Related Art
2,2-Difluoroethylamine is an important intermediate compound in the preparation of active ingredients. The preparation of 2,2-difluoroethylamine (and also tetrafluoroethylamine) using a halo-2,2-difluoroethane compound, namely bromine-2,2-difluoroethane, was described for the first time in 1904 by Swarts in an article with the title “Über einige fluorhaltige Alkylamine” [Concerning a number of fluorine-containing alkylamines] (Chem. Zentralblatt, Volume 75, 1904, pages 944-945). Swarts uses 1-bromo-2,2-difluoroethane and heats it for 3 days in a tube with 2 mol of alcoholic ammonia at 125-145° C. Swarts describes the full conversion of the starting compound into the compounds difluoroethylamine and tetrafluoroethylamine. It is apparent from the article that 2,2-difluoroethylamine is not prepared selectively, since the reaction equally produced tetrafluoroethylamine, which has to be removed. Both products were isolated by fractional distillation or by their conversion into hydrochlorides or oxalates.
More than 50 years later, in fact in 1956, Dickey et al. in Industrial and Engineering Chemistry 1956, No. 2, 209-213, published a process for preparing 2,2-difluoroethylamine that starts from 2,2-difluoro-1 -chloroethane and 28% strength ammonium hydroxide, i.e. 28% strength aqueous ammonia solution. The reactants are reacted in a rocking autoclave. The reaction mixture is heated at temperatures of 135° C. to 140° C. for 31 hours. After the end of the reaction, the reaction mixture is filtered and the amine is removed from the reaction mixture by distillation. However, since there is still a quantity of ammonia and some water in the distillate, the amine is dried over sodium hydroxide and distilled again.
The processes published up to 1956 have the disadvantage that they are not selective, take a very long time, and have a fairly low yield. Aqueous ammonia in combination with the chloride and fluoride ions present in the reaction mixture, and in combination with the high temperatures used in the reactions, is highly corrosive and attacks metallic materials. The processes are therefore not suitable for preparing the desired 2,2-difluoroethylamine in sufficient quantity with cost-effective and environmentally friendly use of resources (e.g. energy and starting materials).
Since that time, no further processes have been published which prepare 2,2-difluoroethylamine using a halo-2,2-difluoroethane compound, particularly 2,2-difluoro-1-chloroethane, and ammonia.
The international patent publication WO2011/012243 (filed as PCT/EP2010/004434) for the first time again described a process for preparing 2,2-difluoroethylamine that starts from 2,2-difluoro-1-haloethane, preferably 2,2-difluoro-1-chloroethane, and ammonia. The process is carried out in the presence of a solvent, and the solvent must not exceed a water content of 15% by volume. The solvent is used in the reaction in an amount of 1 to 50 times, preference being given to an amount of 2 to 20 times. Although the process described in the patent application has distinct advantages over the processes described in 1904 and in 1956, this process is in need of improvement particularly in respect of the environmentally friendly use of resources.
On the basis of the published and unpublished processes for preparing 2,2-difluoroethylamine, the problem now confronted is that of developing a process which starts from 2,2-difluoro-1-chloroethane and ammonia and which avoids the disadvantages identified above.